Stem cell based delivery of IFN-β reduces relapses in experimental autoimmune encephalomyelitis☆

Makar, Tapas K.; Trisler, David; Bever, Christopher T.; Goolsby, James; Sura, K.; Balasubramanian, Shailesh; Sultana, Shireen; Patel, Niraj; Ford, David A.; Singh, Ishwar; Gupta, Aditi; Valenzuela, Reuben; Dhib‐Jalbut, Suhayl

doi:10.1016/j.jneuroim.2008.02.014

Cited by 41 publications

(24 citation statements)

References 52 publications

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“…were initially developed to treat EAE based on the concept that substitution of one or more amino acids to change MHC or -Martin et al, 2003;Pryce et al, 2003;Zajicek et al, 2003;Ni et al, 2004;Maresz et al, 2005;Rog et al, 2005; Freeman et al, 2006;Wissel et al, 2006; Centonze et al, 2007; Collin et al, 2007;Palazuelos et al, 2008;Zhang et al, 2009) Cell-based therapies Neural stem cells Improvement (Picard-Riera et al, 2002; Einstein et al, 2003;Pluchino et al, 2003; Einstein et al, 2006;Makar et al, 2008;Pluchino et al, 2009;Yang et al, 2009) Mesenchymal stem cells Improvement (Zappia et al, 2005; Kassis et al, 2008;Schafer et al, 2008; Bai et al, 2009;Lanza et al, 2009;Lu et al, 2009;Rafei et al, 2009; Freedman et al, 2010;Gordon et al, 2010; Karussis et al, 2010;Yamout et al, 2010) BJP CS Constantinescu et al T-cell receptor (TCR) binding characteristics would induce tolerance to the native peptide through mechanisms including T-cell antagonism and partial agonism as well as cytokine deviation (Evavold and Allen, 1991;Racioppi et al, 1993) and antagonism at the T-cell activation level (De Magistris et al, 1992). Brocke et al induced EAE with a MBP87-99-specific T-cell clone and were able to induce tolerance in vivo by treating mice with an analogue of the native peptide (alanine substitution of the phenylalanine at residue 96).…”

Section: Altered Peptide Ligands Altered Peptide Ligands (Apl) Of Mbpmentioning

confidence: 99%

“…Altered peptide ligands (APL) of MBP were initially developed to treat EAE based on the concept that substitution of one or more amino acids to change MHC or Makar et al, 2008;Pluchino et al, 2009;Yang et al, 2009) Mesenchymal stem cells Improvement (Zappia et al, 2005;Kassis et al, 2008;Schafer et al, 2008;Bai et al, 2009;Lanza et al, 2009;Lu et al, 2009;Rafei et al, 2009;Freedman et al, 2010;Gordon et al, 2010;Karussis et al, 2010;Yamout et al, 2010) BJP CS Constantinescu et al…”

Section: Vla4 Antibodymentioning

confidence: 99%

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Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)

Constantinescu

Farooqi

O’Brien

et al. 2011

British J Pharmacology

1,181

989

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Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro-and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions. LINKED ARTICLESThis article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10. 1111/bph.2011.164.issue-4 Abbreviations ADEM, acute disseminated encephalomyelitis; ADNP, activity dependent neuroprotective protein; AHR, aryl hydrocarbon receptor; APC, antigen-presenting cells; APL, altered peptide ligand; AT, adoptive transfer; C1 and CB2 receptors, cannabinoid receptors 1 and 2; CIS, clinically isolated syndrome; CNS, central nervous system; DA, dark agouti; DMT, disease-modifying treatment; EAE, experimental autoimmune (allergic) encephalomyelitis; EAN, experimental autoimmune (allergic) neuritis; EBV, Epstein-Barr virus; GA, glatiramer acetate; IFN, interferon; IL, interleukin; IL-1RA, interleukin 1 receptor antagonist; JCV, John Cunningham virus; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance imaging; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NABT, normal appearing brain tissue; NAWM, normal appearing white matter; NMO, neuromyelitis optica; NK1 receptor, neurokinin 1 receptor; PGE, prostaglandin E; PLP, proteolipid protein; PP, primary progressive; PR, progressive relapsing; ROR, retinoid orphan receptor; RR, relapsing-remitting; SP, secondary progressive; TCR, T-cell receptor; TGF, transforming growth...

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Section: Altered Peptide Ligands Altered Peptide Ligands (Apl) Of Mbpmentioning

confidence: 99%

Section: Vla4 Antibodymentioning

confidence: 99%

Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)

Constantinescu

Farooqi

O’Brien

et al. 2011

British J Pharmacology

1,181

989

View full text Add to dashboard Cite

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“…45 ) Even more provocatively, our group has developed a means of delivering the IFN␤ gene systemically and to the CNS using bone marrow stem cells as a vehicle. 46 This approach was used successfully in EAE mice and had a therapeutic effect: transduced mice showed diminished inflammation and demyelination, along with a reduction in relapse frequency and severity. The study also demonstrated that IFN␤ achieved its antiinflammatory, immunomodulatory, and neuroprotective effects by the regulation of cell adhesion molecules, cytokine profile, growth factor release, and neural apoptosis and regeneration.…”

Section: Cns Immune Effects Of Ifn␤mentioning

confidence: 99%

Interferon-β mechanisms of action in multiple sclerosis

Dhib‐Jalbut¹,

Marks²

2010

Neurology

265

113

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Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS characterized by inflammation, demyelination, and axonal injury. These pathologic effects are manifested in clinical symptoms of relapse and disability. Various disease-modifying therapies have been developed in recent years to modulate the body's immune response. Among the most widely used are the beta interferons (IFNbeta). All produce comparable biological effects and are approved for the treatment of relapsing-remitting MS (RRMS). Although the precise mechanisms through which IFNbeta achieves its antiinflammatory and immunomodulatory effects remain uncertain, several modes of action have been proposed, including inhibition of T-cell activation and proliferation; apoptosis of autoreactive T cells; induction of regulatory T cells; inhibition of leukocyte migration across the blood-brain barrier; cytokine modulation; and potential antiviral activity. Endogenously produced IFNbeta in the injured brain is also now believed to contribute to mediation of antiinflammatory and regenerative effects. All these mechanisms are believed to underlie the therapeutic effect of IFNbeta in the treatment of RRMS.

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“…In another report, a method is described for delivery of the IFN-gene in EAE both systemically and into the CNS using bone marrow stem cells as a vehicle. In these experiments, mice transplanted with IFN--engineered bone marrow stem cells showed a significant inhibition of EAE onset, and reduced overall severity of the disease compared with the control group [102].…”

Section: Treatment Of Msmentioning

confidence: 85%

Mouse Models of Autoimmune Diseases

Marques

Müller²

2009

CDDT

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Significant progress has been made in past decades in our understanding of the basic mechanisms underlying autoimmune diseases. Nevertheless, many questions remain unanswered, in particular regarding the mechanisms at very early stages of these diseases. Reliable animal models are of crucial importance in basic research and may help us to understand central disease pathways. They are also indispensable for pre-clinical drug testing. Here we present and discuss two mouse models of rheumatoid arthritis and multiple sclerosis, respectively. In experimental studies using the models of collagen-induced arthritis and experimental autoimmune encephalomyelitis, the efficacy of new biological agents has been tested, which paved the way for clinical trials. A further interesting field where mouse models may provide valuable informations, is the identification of susceptibility genes for autoimmune diseases. Overall, in some instances studies with inbred strains may have an advantage over human studies, because environmental factors may easily be controlled and the genetic differences between different mouse strains are better characterized.

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Stem cell based delivery of IFN-β reduces relapses in experimental autoimmune encephalomyelitis☆

Cited by 41 publications

References 52 publications

Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)

Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)

Interferon-β mechanisms of action in multiple sclerosis

Mouse Models of Autoimmune Diseases

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